Plastics has developed along with the progress of chemistry and, as being highly functional materials used in every field as a substitute for metal, belongs to the indispensable materials of today. Plastics finds settled application as industrial materials in commodities and various other products, and the range of applications thereof is being widely enlarged, from nuclear power-related uses to space and ocean developments. Plastics is the materials which are possessed of prominent properties and potentials unique to other materials, and is characterized by a reduced weight, moldability, capability to be formed into a product of complicated shape in fewer steps, a high corrosion resistance, an improved resistance to chemical attack, and so forth. While the heat resistance of plastics used to be poor as compared with metal, design and development of a novel, heat-resistant polymeric material took off in the 1960s, and polymeric materials of high strength and high modulus of elasticity have been developed. The polymeric materials are called engineering plastics, and generally defined as having such a performance that the heat deformation temperature is 100° C. or higher, the tensile strength is not less than 60 MPa, and the modulus of elasticity is not less than 2 GPa.
During the development of liquid-crystalline engineering plastics, the inventors of the present invention focused attention on 4-hydroxycinnamic acid (4HCA) as a reactive plant-derived rigid substance. Few researches existed on 4HCA homopolymer (poly-4HCA), and they were directed solely to the synthesis of the polymer, and polymer particles. The inventors of the present invention found for the first time that poly-4HCA as one of polyesters of natural origin has nematic liquid-crystalline properties. Poly-4HCA was photoreactive and biocompatible, and had the heat resistance as required of engineering plastics, but was brittle, and poor in solubility and processability. Such problems with the polymer were considered to be caused by a low molecular weight, and a high rigidity of the molecular backbone of the polymer.
With this being the situation, the inventors thought of copolymerization with a natural product imparting flexibility to the backbone of poly-4HCA, and focused on 3,4-dihydroxycinnamic acid (caffeic acid: DHCA) as a 4HCA derivative. In the presence of acetic anhydride as a transesterification agent and sodium acetate as a catalyst, 4HCA and DHCA were heated at 200° C. for six hours to polycondense them so as to obtain a DHCA-4HCA copolymer. The copolymer as obtained was solid at 25° C. in spite of DHCA contained in the copolymer. When, however, the copolymer was heated, a banding pattern was distinctly observed, that is to say, the copolymer exhibited its flowing property, so that it was confirmed that the copolymer was liquid crystal. The liquid crystallization temperature decreased to 150° C. in accordance with the increase in compositional ratio of DHCA, while the weight reduction temperature exceeded 300° C. As a consequence, the copolymer was easy to handle because of its enlarged temperature range of liquid crystallization (Non-Patent Literature 1).
In addition, the inventors of the present invention succeeded in increasing the molecular weight of a DHCA-4HCA copolymer that strongly influences the strength and the modulus of elasticity of the copolymer. To be more specific: When a compression test was conducted on the resultant DHCA-4HCA copolymer with respect to the strength and the modulus of elasticity, each varying with the compositional ratio of the copolymer, the test results showed that the copolymer was comparable to polycarbonate as a representative of engineering plastics for general purpose use in breaking strength and Young's modulus of elasticity if it contained 50 to 100 mol % DHCA (Patent Literature 1).
Hydrophilic block copolymers or graft copolymers generally form micelles in water through self-organization. It is known that the micelle as formed through self-organization has an internal hydrophobic core and external hydrophilic groups. The micelle-forming copolymer which is biocompatible is used as a sustained drug release material because the copolymer encapsulates a drug in the hydrophobic cores of its micelles, and improves the dispersibility of the drug in the blood by the action of the hydrophilic groups outside the core. The sustained drug release material as such is considered to carry a lot of potential for migration into the blood, and so forth if made nanoparticulate. The biocompatibility should refer to a property of suppressing non-specific adsorption of a substance of biological origin, such as protein, being non-cytotoxic, non-antigenic, and non-inflammatory, being stable in the blood or other body fluids, and so forth.
Nanoparticles are commonly sensitive to such external factors as temperature, pH, electromagnetic field, and light, whereupon those having an unsaturated bond are receiving special attention as the nanoparticles which are easily and quickly controllable in material properties as appropriate to individual uses because of their photoreactivity. For instance, researches have been conducted on various situations including the application of poly-4HCA or 4HCA copolymer because 4HCA and its derivatives having unsaturated bonds are known for their crosslinking polymerization by ultraviolet light.
The inventors of the present invention already succeeded in producing nanoparticles by causing the self-organization of poly-4HCA and DHCA homopolymer in a solvent. They demonstrated that the nanoparticles as produced were photoreactive, were hydrolyzed under alkaline conditions, and had an interesting variation in particle size. A problem with nanoparticles of DHCA-4HCA copolymers, however, still exists in that such nanoparticles are not applicable to a medical material such as drug delivery system due to their high hydrophobicity preventing them from being dispersed in an aqueous solution.